Wilms tumor is the most common kidney tumor of childhood and has served as an important model for understanding the genetics and molecular biology of cancer. Epidemiologic studies have suggested but not proven an environmental influence. We propose to conduct the first large, comprehensive case-control study of risk factors for Wilms tumor. The proposed study will incorporate improved methods for exposure measurement and clinical and biologic markers to evaluate potential gene-environment interaction. About 800 cases will be identified through the National Wilms Tumor Study Group (NWTSG), a national collaborative clinical trial that enrolls over 95% of all cases of Wilms tumor diagnosed in the United States. Parents of cases and of 800 controls identified by random digit telephone dialing, matched to cases on age and geographic area, will be interviewed by telephone. A major aim of the study is to clarity the role of parental occupation in the etiology of Wilms tumor. Paternal employment as welders or mechanics and exposure to metals and solvents have been associated with Wilms tumor. Implicated maternal occupations include hairdressers, laboratory workers, and dental assistants. However, previous studies have been limited by a number of methodologic problems, most notably the inability to accurately assess occupational exposures. The proposed study uses a recently developed system of branched interviews and industrial hygienist review to obtain job- and exposure-specific data. Since most of the patients have data collected on clinical and biologic markers as part of the ongoing NWTS-5 therapeutic and biology study, we will analyze the exposures separately for subgroups of patients defined by loss of heterozygosity at 11p, age at diagnosis, precursor lesions, and presence of congenital anomalies. We will be able to define subgroups with potential de novo germline mutations, an etiologic pathway more likely to be influenced by paternal preconceptional occupational exposures. We will also evaluate other suspected but unproven risk factors for Wilms tumor, such as residential use of pesticides, pregnancy conditions and exposures, and neonatal and childhood conditions. A medical records validation will be performed for pregnancy and delivery factors. This study will provide important new advances in our understanding of Wilms tumor given the study size, quality of exposure assessment, and incorporation of clinical and biological markers of etiologic heterogeneity.